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Safety and Efficacy Study of an Anti-CD20 Monoclonal Antibody (AME-133v) to Treat Non-Hodgkin's Lymphoma

This study is currently recruiting participants.
Verified by Applied Molecular Evolution, March 2008

Sponsored by: Applied Molecular Evolution
Information provided by: Applied Molecular Evolution
ClinicalTrials.gov Identifier: NCT00354926
  Purpose

The protein engineering of AME-133v is hypothesized to result in an anti-CD20 therapy with greater potency and efficacy in all patients, but particularly in genetically defined subpopulations that respond poorly to rituximab because they express a low affinity version of the Fc receptor on their immune effector cells. A monoclonal antibody that has increased binding for this receptor should be more effective in stimulating effector cell killing and thus improve response to the antibody. This study is designed to provide evidence of the safety and a preliminary understanding of the efficacy of AME 133v.


Condition Intervention Phase
Non-Hodgkin's Lymphoma
Drug: AME-133v (LY2469298)
Phase I
Phase II

MedlinePlus related topics:   Lymphoma  

ChemIDplus related topics:   Rituximab  

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:   Open-Label, Multicenter, Phase 1/2 Dose-Escalation Study of AME-133v (LY 2469298), Administered Intravenously in Four Weekly Doses, in Subjects With CD20+ Follicular Relapsed or Refractory Non-Hodgkin's Lymphoma

Further study details as provided by Applied Molecular Evolution:

Primary Outcome Measures:
  • Adverse events and laboratory evaluations

Secondary Outcome Measures:
  • Pharmacokinetic analysis and tumor evaluation by International Workshop criteria

Estimated Enrollment:   80
Study Start Date:   July 2006

  Eligibility
Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Criteria

Inclusion Criteria:

To be included in the study protocol, subjects have to meet all of the following criteria.

  • Have morphologically confirmed diagnosis of CD-20+ follicular B-cell non-Hodgkin's lymphoma;
  • Have the low affinity form of FcγRIIIa (F/F or F/V at position 158) as determined by FcR genotyping;
  • Have measurable disease. Measurable masses (such as enlarged lymph nodes) must have a clearly defined bi-dimensional diameter of at least 1.5 x 1.5 cm on physical examination or ≤ 1.5 cm in one of the dimensions by CT, MRI, or plain radiograph;
  • Have received prior treatment with chemotherapy given without rituximab; OR, Have not relapsed or progressed within 120 days (inclusive) of the last infusion of rituximab;
  • Be 18 years of age or greater;
  • Have a negative pregnancy test, if relevant. Women of childbearing potential (not postmenopausal for at least one year and not surgically incapable of bearing children) must agree not to become pregnant for the duration of the study. To do this, they must agree to use a medically acceptable contraceptive regimen;
  • Have a performance status of 0 to 2 on the ECOG performance scale;
  • Have adequate hematopoietic, renal, and hepatic function defined as:

    1. Absolute neutrophil count greater than 1,500/mm³;
    2. Platelet count greater than 75,000/mm³;
    3. Hemoglobin at least 8 g/dL;
    4. Serum creatinine ≤ 1.5x upper limit of normal;
    5. Total bilirubin ≤ 1.5x upper limit of normal;
    6. ALT ≤ 1.5 x upper limit of normal;
    7. Alkaline phosphatase ≤ 1.5x upper limit of normal.
  • No evidence of hepatitis B or C infection (no detectable HBV DNA or HCV RNA);
  • Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, or other investigational therapy for at least 30 days prior to study enrollment;
  • Have discontinued all high-dose corticosteroid therapy at least 30 days prior to study enrollment (≤ 10 mg/day of Prednisone or equivalent is allowable);
  • Have life expectancy of more than 3 months;
  • Be able to give written informed consent.

Exclusion Criteria:

Subjects with any of the following exclusions are not allowed to participate in the study.

  • Allergy to monoclonal antibodies or any of the study drug components;
  • Concurrent malignancy that could complicate interpretation of response evaluation, including any histologic evidence of diffuse B-cell lymphoma. Non-melanoma skin cancer and carcinoma in situ of the cervix are not exclusions;
  • Significant cardiac disease (e.g. NYHA CHF of class III or IV, history of MI within one year prior to study Day 1, unstable angina, uncontrolled hypertension, clinically significant cardiac arrhythmia (CTCAE Grade 2 or higher), or clinically significant baseline ECG or MUGA abnormality.
  • Positive test for serum cardiac troponins (cTnI or cTnT assay; special processing required, and the same assay must be used throughout the study; see Study Reference Manual)
  • Active infection requiring oral or i.v. antibiotics;
  • Administration of blood transfusions or red blood cell growth factors within 10 days preceding enrollment into the protocol;
  • Administration of white cell growth factors within 28 days preceding enrollment into the protocol;
  • Concomitant nonmalignant disease(s) which could interfere with implementation of the protocol, make the study results difficult to interpret, or which represent additional safety risks;
  • History of HIV-associated non-Hodgkin's lymphoma.
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00354926

Contacts
Contact: Susan Carpenter, PhD     858-597-4990     carpentersu@lilly.com    

Locations
United States, Alabama
University of Alabama Medical Center     Recruiting
      Birmingham, Alabama, United States, 35249
      Contact: Alma DelGrosso, RN, OCN, CCRP     205-934-0337     alma.delgrosso@ccc.uab.edu    
      Principal Investigator: Andres Forero-Torres, MD            
United States, California
UCLA Medical Hematology and Oncology     Recruiting
      Los Angeles, California, United States, 90095
      Contact: Shu-Shanna Dixon     310-825-3459     ssdixon@mednet.ucla.edu    
      Principal Investigator: Sven de Vos, M.D., Ph.D.            
Stanford University Medical Center     Recruiting
      Stanford, California, United States, 94305
      Contact: Julia Dugay, MD     650-725-6413     jdugay@stanford.edu    
      Principal Investigator: Kristen Ganjoo, MD            
United States, Illinois
Rush University Medical Center     Recruiting
      Chicago, Illinois, United States, 60612
      Contact: Wendy Mallon, RN, BSN, OCN     312-563-2140     wendy_mallon@rush.edu    
      Principal Investigator: Stephanie A. Gregory, MD            
United States, Iowa
University of Iowa     Recruiting
      Iowa City, Iowa, United States, 52242
      Contact: Mary Shannon     319-356-3516     mary-shannon@uiowa.edu    
      Principal Investigator: Brian Link, M.D.            
United States, Nevada
Nevada Cancer Institute     Recruiting
      Las Vegas, Nevada, United States, 89135
      Contact: Christine Zades     702-822-5456     czades@nvcancer.org    
      Principal Investigator: Nam Dang, MD            
United States, Ohio
Cleveland Clinic Foundation     Recruiting
      Cleveland, Ohio, United States, 44195
      Contact: Stacy Mathews     216-445-6470     MATHEWS@ccf.org    
      Contact: Randall Davis     216.444.9270     davisr5@ccf.org    
      Principal Investigator: Brad Pohlman, MD            
United States, Pennsylvania
Fox Chase Cancer Center     Recruiting
      Philadelphia, Pennsylvania, United States, 19111
      Contact: Linda Thibodeau     215-728-2207     linda.thibodeau@fccc.edu    
      Principal Investigator: Mitchell R. Smith, MD, PhD            
University of Pittsburgh Medical Center     Recruiting
      Pittsburgh, Pennsylvania, United States, 15232
      Contact: Patricia Schaefer, RN, BSN     412-623-4881     schaeferpm@upmc.edu    
      Principal Investigator: Kenneth Foon, MD            
United States, Tennessee
Sarah Cannon Research Institute     Recruiting
      Nashville, Tennessee, United States, 37203
      Contact: Carla Mazzone     615-329-7274        
      Principal Investigator: Ian W. Flinn, MD, PhD            
United States, Virginia
University of Virginia Health System     Recruiting
      Charlottesville, Virginia, United States, 22908
      Contact: Susan Hamil, RN, BSN, OCN     434-924-5254     shs3s@virginia.edu    
      Principal Investigator: Michael E. Williams, MD            

Sponsors and Collaborators
Applied Molecular Evolution

Investigators
Principal Investigator:     Brian Link, MD     University of Iowa    
Principal Investigator:     Andres Forero-Torres, MD     University of Alabama Medical Center    
Principal Investigator:     Nam Dang, MD     Nevada Cancer Institute    
Principal Investigator:     Sven de Vos, MD, PhD     University of California, Los Angeles    
Principal Investigator:     Kristen Ganjoo, MD     Stanford University    
Principal Investigator:     Brad Pohlman, MD     The Cleveland Clinic    
Principal Investigator:     Mitchell R. Smith, MD, PhD     Fox Chase Cancer Center    
Principal Investigator:     Michael E. Williams, MD     University of Virginia Health Systems    
Principal Investigator:     Ian Flinn, MD, PhD     Sarah Cannon Research Institute    
Principal Investigator:     Kenneth Foon, MD     University of Pittsburgh    
Principal Investigator:     Stephanie A. Gregory, MD     Rush University Medical Center    
  More Information

Study ID Numbers:   AME 06.133v.A
First Received:   July 18, 2006
Last Updated:   March 3, 2008
ClinicalTrials.gov Identifier:   NCT00354926
Health Authority:   United States: Food and Drug Administration

Keywords provided by Applied Molecular Evolution:
Non-Hodgkin's Lymphoma  
rituximab  
humanized monoclonal antibody  
anti-CD20 monoclonal antibody  

Study placed in the following topic categories:
Antibodies, Monoclonal
Lymphatic Diseases
Antibodies
Immunoproliferative Disorders
Rituximab
Lymphoma, small cleaved-cell, diffuse
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Lymphoma

Additional relevant MeSH terms:
Neoplasms
Hemic and Lymphatic Diseases
Neoplasms by Histologic Type
Immunologic Factors
Immune System Diseases
Antineoplastic Agents
Therapeutic Uses
Physiological Effects of Drugs
Antirheumatic Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 08, 2008